Purinergic receptors can be classified into the P.sub.1 (adenosine) receptors and the P.sub.2 (adenosine 5' triphosphate) receptors. Adenosine receptors can further be delineated into major subclasses, the A.sub.1, A.sub.2 (A.sub.a2 and A.sub.a2b) and A.sub.3 adenosine receptors. These subtypes are differentiated by molecular structure, radioligand binding profiles, and by pharmacological and functional activity. Binding of adenosine, a naturally occurring nucleoside, to specific adenosine receptors leads to either stimulation (A.sub.2 -receptor activation) or inhibition (A.sub.1 -receptor activation) of adenylate cyclase activity resulting in an increase or decrease of intracellular cAMP, respectively. Most tissues and cell types possess either the A.sub.1 or A.sub.2 receptor, or both. Moreover, A.sub.1 adenosine receptors have been identified in the nuclear fraction of splenocytes (Donnabella, Life Sci. 46:1293 (1990)). Specific A.sub.1, A.sub.2, and A.sub.3 antagonists and agonists are well-known in the art. See, e.g., Trivedi et al., Structure-Activity Relationships of Adenosine A.sub.1 and A.sub.2 Receptors, In: Adenosine and Adenosine Receptors, M. Williams, Ed., Humana Press, Clifton, N.J., USA (1990); Jacobson et al., J. Medicinal Chem. 35:407 (1992); Fredholm et al., Pharm. Rev. 46:143 (1994); Jacobson, Abstracts from Purines '96, Drug Dev. Res., March 1996, page 112. Divalent ions (Mg.sup.2+ and Ca.sup.2+) and allosteric enhancers enhance the binding of A.sub.1 adenosine receptor agonists to A.sub.1 adenosine receptors (Kollias-Baker, Circ. Res. 75:961 (1994)). Allosteric enhancers enhance A.sub.1 receptor mediated responses and are described in Bhattacharya, Biochim. Biophys. Acta 1265:15 (1995).
Inflammatory cells, including monocytes and alveolar macrophages are known to express the A.sub.1, A.sub.2 and A.sub.3 receptor subtypes. Eppell et al., J. Immunology 143:4141 (1989); Lapin and Whaley, Clin. Exp. Immunol. 57:454 (1984); Saijadi, et al., J. Immunol. 156:3435 (1996). Activation of the A.sub.3 or A.sub.2 receptors has been shown to inhibit monocyte function.
Mature monocytes enter the circulatory system from the bone marrow; some monocytes enter tissues and develop into macrophages in the spleen, lymph nodes, liver, lung, thymus, peritoneum, nervous system, skin and other tissues. Monocytes and macrophages can be identified by morphology, cell surface antigens, and the presence of characteristic enzymes. Both monocytes and macrophages play a role in inflammatory responses by eliminating bacteria and other pathogens by phagocytosis. Monocytes and macrophages also secrete various proteins active in immune and inflammatory responses, including Tumor Necrosis Factor (TNF) and Interleukin I (IL-1)). Upon stimulation, monocytes and macrophages can generate various oxygen metabolites, including superoxide anion and H.sub.2 O.sub.2 that are toxic to both pathogens and normal cells.